Molnupiravir for intra-household prevention of COVID-19: The MOVe-AHEAD randomized, placebo-controlled trial
Authors: Sady A. Alpizar, Jose Accini, Duane C. Anderson, Basem Eysa, Isaí Medina-Piñón, Norio Ohmagari, Mykola M. Ostrovskyy, Angela Aggrey-Amable, Karen Beck, Dana Byrne, Staci Grayson, Peggy M.T. Hwang, Julia D. Lonchar, Julie Strizki, Yayun Xu, Amanda Paschke, Carisa S. De Anda, Pamela S. Sears
Journal: Journal of Infection (2023)

•Phase 3 trial evaluating molnupiravir for post-exposure prophylaxis of COVID-19. •About 84% of the trial population had anti-SARS-CoV2 antibodies at baseline. •Day 14 COVID-19 rates (molnupiravir 6.5%, placebo 8.5%) were similar between arms. •Onset of COVID-19 was mostly after the end of therapy in the molnupiravir arm. •Molnupiravir was well-tolerated but did not meet the superiority criterion. Objectives To evaluate efficacy and safety of molnupiravir for intra-household post-exposure prophylaxis (PEP) of COVID-19. Methods MOVe-AHEAD was a randomized, controlled, double-blind, phase 3 trial comparing molnupiravir (800 mg twice daily for 5 days) with placebo. Eligible participants were adult, unvaccinated, asymptomatic household contacts of patients with laboratory-confirmed COVID-19. The primary efficacy endpoint was the incidence of COVID-19 through day 14 in modified intention-to-treat (MITT) participants (those who received ≥1 dose of study intervention) without detectable SARS-CoV-2 at baseline, termed the MITT-VN population. Superiority of molnupiravir was prespecified as a stratified one-sided p-value of <0.0249 for the treatment difference in this endpoint. Results The MITT population comprised 763 participants randomized to molnupiravir and 764 to placebo; 83.6% had anti-SARS-CoV-2 antibodies at baseline. In the MITT-VN population, COVID-19 rates through day 14 were 6.5% with molnupiravir and 8.5% with placebo (one-sided p-value: 0.0848). In the molnupiravir arm, 25/35 COVID-19 events (71%) occurred after completion of treatment (versus 17/49 [35%] for placebo). Adverse event rates were low and similar between molnupiravir and placebo. Conclusions Molnupiravir was well-tolerated but did not meet the prespecified superiority criterion, possibly influenced in part by the high pre-existing immunity in the trial population. To evaluate efficacy and safety of molnupiravir for intra-household post-exposure prophylaxis (PEP) of COVID-19. MOVe-AHEAD was a randomized, controlled, double-blind, phase 3 trial comparing molnupiravir (800 mg twice daily for 5 days) with placebo. Eligible participants were adult, unvaccinated, asymptomatic household contacts of patients with laboratory-confirmed COVID-19. The primary efficacy endpoint was the incidence of COVID-19 through day 14 in modified intention-to-treat (MITT) participants (those who received ≥1 dose of study intervention) without detectable SARS-CoV-2 at baseline, termed the MITT-VN population. Superiority of molnupiravir was prespecified as a stratified one-sided p-value of <0.0249 for the treatment difference in this endpoint. The MITT population comprised 763 participants randomized to molnupiravir and 764 to placebo; 83.6% had anti-SARS-CoV-2 antibodies at baseline. In the MITT-VN population, COVID-19 rates through day 14 were 6.5% with molnupiravir and 8.5% with placebo (one-sided p-value: 0.0848). In the molnupiravir arm, 25/35 COVID-19 events (71%) occurred after completion of treatment (versus 17/49 [35%] for placebo). Adverse event rates were low and similar between molnupiravir and placebo. Molnupiravir was well-tolerated but did not meet the prespecified superiority criterion, possibly influenced in part by the high pre-existing immunity in the trial population.